Florida ranks third in HIV cases in the US, in part due to the association of cocaine abuse with risky sexual behavior and transmission of HIV-1. Although HIV-1 infection treated with cART is now a chronic disease, HIV- related co-morbidities such as cardiovascular disease (CVD) have emerged as a new challenge, particularly among HIV infected - cocaine abusers. Conventional methods to determine CVD risk, e.g., Framingham Risk Scores, may not be as effective in identifying risk in this younger, HIV- infected group as these methods do not take into consideration abnormalities in the inflammatory pathways, cardiac endothelial functions, endocrines and immune activation that occur in HIV and cocaine abuse. This application hypothesizes that HIV-1 infection and cocaine abuse lead to a higher risk of developing CVD due to disturbances in these biomarkers and that the conventional ADA /NCEP based standard of care (SOC) may be less effective in reducing CVD risk in this population. To test this hypothesis, this 5-year application proposes to conduct a cross-sectional investigation of a total of 600 men and women, African Americans, Caucasians, and Hispanics, in 4 groups: HIV-1+ -cocaine abusers (n=200); HIV-1- -cocaine abusers (n=100); HIV-1+ - non- cocaine abusers (n=100); and, HIV-1- - non-cocaine abusers, control, (n=200). All participants will undergo measurement of carotid artery intima-media thickness (IMT), and those identified at high risk of CVD will be referred for SOC treatment and re-assessed after 24 months. AIM 1: To conduct carotid IMT measurement among HIV-1+ cocaine abusers, HIV-1- cocaine abusers, HIV-1+ non-cocaine abusers, HIV-1- non-cocaine abusers (control). AIM2: To evaluate insulin resistance, inflammatory and immunologic biomarkers, and endothelial progenitor cells as predictors of CVD risk, as defined by IMT: a: To investigate insulin resistance among HIV-1+ cocaine abusers, HIV-1- cocaine abusers, HIV-1+ non-cocaine abusers, HIV-1- non-cocaine abusers (control). b: To investigate inflammatory markers (plasma CRP, IL-1, IL-6, and TNF-?) among HIV-1+ cocaine abusers, HIV-1- cocaine abusers, HIV-1+ non-cocaine abusers, HIV-1- non-cocaine abusers (control). c: To investigate the surrogate markers of immune activation, sCD14, sCD163 and LPS, among HIV- 1+ cocaine abusers, HIV-1- cocaine abusers, HIV-1+ non-cocaine abusers, HIV-1- non-cocaine abusers. d: To investigate circulating endothelial progenitor cells, EPCs, (CD34+ -VEGFR+), circulating immature-endothelial progenitor cells (CD133+ - VEGFR+), and levels of plasma VEGFR in all study groups. AIM 3: To compare the response to ADA/NCEP SOC intervention at 24 months by study group (HIV-1+ - cocaine abusers, HIV-1- cocaine abusers, HIV-1+ non-cocaine abusers, HIV-1- non-cocaine abusers) evaluating biomarkers (insulin, immune activation, progenitor cells) and IMT.